A Pilot Study on Neuroimaging in SCD: Part of The Boston Consortium to Cure Sickle Cell Disease

• ClinicalTrials.gov Identifier: NCT04166526
• Recruitment Status: Recruiting
• First Posted: November 18, 2019
• Last Update Posted: August 11, 2022
• Sponsor: Boston Children's Hospital
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by (Responsible Party): Ellen Grant, Boston Children's Hospital

Tracking Information

• First Submitted Date: October 15, 2019
• First Posted Date: November 18, 2019
• Last Update Posted Date: August 11, 2022
• Actual Study Start Date: October 25, 2019
• Estimated Primary Completion Date: May 1, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 14, 2019)

Accuracy of FDNIRS-DCS in measuring blood oxygenation of the brain [ Time Frame: 6 months ]

Blood oxygenation of the brain will be measured using FDNIRS-DCS techniques and then compared with data from a simultaneous MRI scan.

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Pilot Study on Neuroimaging in SCD: Part of The Boston Consortium to Cure Sickle Cell Disease
• Official Title: A Pilot Study on Neuroimaging in SCD: Part of The Boston Consortium to Cure Sickle Cell Disease

Brief Summary

Sickle Cell Disease (SCD) impairs oxygen transport to tissue and causes endothelial injury. Thus, therapeutic interventions aim to improve both, but there is an unmet need for biomarkers to determine when intervention is necessary and evaluate the effectiveness of the chosen intervention in individual patients. This study proposes to monitor SCD and its treatment through their impact on cerebral hemodynamics, as the brain is one of the most vulnerable and consequential targets of the disease. Specifically, this study will optimize quantitative magnetic resonance imaging (MRI) and advanced optical spectroscopy techniques such as frequency-domain near-infrared and diffuse correlation spectroscopies (FDNIRS-DCS) to monitor 1) cerebral oxygen transport with measures of cerebral blood flow (CBF), cerebral oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen consumption (CMRO2) and 2) endothelial function with cerebrovascular reactivity (CVR).

Additionally, this study aims to monitor baseline cerebral oxygen transport and CVR, as well as changes that occur with treatment (transfusion or genetic therapy to induce fetal hemoglobin) and assess hemoglobinopathy patients with known genotypes and phenotypes. The ultimate goal is to demonstrate the potential of this monitoring approach to select individual SCD subjects for interventions and evaluate individual responses to treatment. Success will help justify inclusion of these modalities in ongoing and future clinical trials of novel SCD therapies.

• Detailed Description: Not Provided
• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: In this pilot study, investigators plan on recruiting 8 children between the ages of 8-18 from hematology clinics.
• Condition: Sickle Cell Disease

Intervention

• Device: FDNIRS-DCS
  FDNIRS-DCS measurements will be performed at the same time as all MRI scans. Participants in Group 4 will have additional measurements before, during, and after the their scheduled transfusion.
  Other Name: Frequency-Domain Near-Infrared and Diffuse Correlation Spectroscopy
• Device: MRI
  Participants in Groups 1-3 will receive a single, hour-long MRI. Participants in Group 4 will receive two, one hour long MRI scans: one within a week prior to their transfusion and one within a week after their transfusion.
  Other Name: Magnetic Resonance Imaging

Study Groups/Cohorts

• Group 1: Typically developing children
  Participants of this group will not have a diagnosis of SCD. These participants will undergo an MRI, lasting approximately an hour, with simultaneous FDNIRS-DCS monitoring.
  Interventions:

  • Device: FDNIRS-DCS
  • Device: MRI
• Group 2: Children with SCD not receiving treatment
  Participants of this group have a diagnosis of SCD, but do not receive chronic transfusions, gene therapy or bone marrow transplants. These participants will undergo an MRI, lasting approximately an hour, with simultaneous FDNIRS-DCS monitoring.
  Interventions:

  • Device: FDNIRS-DCS
  • Device: MRI
• Group 3: Children with SCD who have undergone gene therapy
  Participants of this group have a diagnosis of SCD and have had gene therapy at least one month prior to enrollment. These participants will undergo an MRI, lasting approximately an hour, with simultaneous FDNIRS-DCS monitoring.
  Interventions:

  • Device: FDNIRS-DCS
  • Device: MRI
• Group 4: Children with SCD who have chronic transfusions
  Participants of this group have a diagnosis of SCD and receive chronic transfusions. These participants will undergo an MRI, lasting approximately an hour, with simultaneous FDNIRS-DCS monitoring.
  Interventions:

  • Device: FDNIRS-DCS
  • Device: MRI

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 14, 2019): 8
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 1, 2025
• Estimated Primary Completion Date: May 1, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

Group 1 (healthy controls):

• Children ages 8-18 without SCD

Group 2 (SCD patients without treatment):

• SCD patients ages 8-18 who:

  • have not undergone gene therapy or a bone marrow transplant
  • are not receiving chronic transfusions
  • have not received a blood transfusion in the past 3 months

Group 3 (SCD patients who have undergone gene therapy):

• SCD patients ages 8-18 who have had gene therapy at least one month prior to enrollment

Group 4 (SCD patients who have chronic transfusions):

• SCD patients ages 8-18 who receive chronic transfusions

Exclusion Criteria:

• Electrical implants such as cardiac pacemakers or perfusion pumps;
• Ferromagnetic implants such as aneurysm clips, surgical clips, prosthesis, artificial hearts, valves with steel parts, metal fragments, shrapnel, tattoos near the eye, or steel implants;
• Ferromagnetic objects such as jewelry or metal clips;
• Women of childbearing age who are seeking to become pregnant, who are breastfeeding, or who suspect they may be pregnant;
• Pre-existing medical conditions including a likelihood of developing seizures or claustrophobic reactions;
• Any greater than normal potential for cardiac arrest;
• Subjects requiring sedation for MRI

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 8 Years to 18 Years (Child, Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Ellen Grant, MD; 857-218-5111; Ellen.Grant@childrens.harvard.edu

Contact: Katherine Eident, BS; 617-355-2184; katherine.eident@childrens.harvard.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04166526
• Other Study ID Numbers: IRB-P00033322; 1OT2HL152640-01 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Ellen Grant, Boston Children's Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: Boston Children's Hospital
• Original Study Sponsor: Same as current
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Ellen Grant, MD; Boston Children's Hospital

• PRS Account: Boston Children's Hospital
• Verification Date: August 2022